The impact of statin treatment on presentation mode and early outcomes in acute coronary syndromes

OBJECTIVES: The role of statin use in the treatment of acute coronary syndromes (ACS) is not clear. The aim of our study was to evaluate the role of statins in ACS. METHODS: Using data from the Acute Myocardial Infarction in Switzerland (AMIS Plus) Project, we compared the effects of chronic statin use, statin therapy after admission and no statin therapy on presentation mode and outcomes in ACS. RESULTS: Available data from the period 2001-2006 including 11,603 patients were analyzed. Major cardiac event rates and in-hospital mortality were more common in statin-naive patients compared to patients who received statins. CONCLUSIONS: Our results support the importance of statin treatment in ACS. Chronic statin therapy seems to alter the initial presentation of ACS but it is questionable whether it provides an additional effect on early outcomes compared to the establishment of statin therapy after admission in statin-naive patients.

Impact of preservation solution on the extent of blood-air barrier damage and edema formation in experimental lung transplantation

A major aim in lung transplantation is to prevent the loss of structural integrity due to ischemia and reperfusion (I/R) injury. Preservation solutions protect the lung against I/R injury to a variable extent. We compared the influence of two extracellular-type preservation solutions (Perfadex, or PX, and Celsior, or CE) on the morphological alterations induced by I/R. Pigs were randomly assigned to sham (n = 4), PX (n = 5), or CE (n = 2) group. After flush perfusion with PX or CE, donor lungs were excised and stored for 27 hr at 4 degrees C. The left donor lung was implanted into the recipient, reperfused for 6 hr, and, afterward, prepared for light and electron microscopy. Intra-alveolar, septal, and peribronchovascular edema as well as the integrity of the blood-air barrier were determined stereologically. Intra-alveolar edema was more pronounced in CE (219.80 +/- 207.55 ml) than in PX (31.46 +/- 15.75 ml). Peribronchovascular (sham: 13.20 +/- 4.99 ml; PX: 15.57 +/- 5.53 ml; CE: 31.56 +/- 5.78 ml) and septal edema (thickness of alveolar septal interstitium, sham: 98 +/- 33 nm; PX: 84 +/- 8 nm; CE: 249 +/- 85 nm) were only found in CE. The blood-air barrier was similarly well preserved in sham and PX but showed larger areas of swollen and fragmented epithelium or endothelium in CE. The present study shows that Perfadex effectively prevents intra-alveolar, septal, and peribronchovascular edema formation as well as injury of the blood-air barrier during I/R. Celsior was not effective in preserving the lung from morphological I/R injury.

Impact of a self-developed planning and self-constructed navigation system on skull base surgery: 10 years experience

CONCLUSION: Our self-developed planning and navigation system has proven its capacity for accurate surgery on the anterior and lateral skull base. With the incorporation of augmented reality, image-guided surgery will evolve into 'information-guided surgery'. OBJECTIVE: Microscopic or endoscopic skull base surgery is technically demanding and its outcome has a great impact on a patient's quality of life. The goal of the project was aimed at developing and evaluating enabling navigation surgery tools for simulation, planning, training, education, and performance. This clinically applied technological research was complemented by a series of patients (n=406) who were treated by anterior and lateral skull base procedures between 1997 and 2006. MATERIALS AND METHODS: Optical tracking technology was used for positional sensing of instruments. A newly designed dynamic reference base with specific registration techniques using fine needle pointer or ultrasound enables the surgeon to work with a target error of < 1 mm. An automatic registration assessment method, which provides the user with a color-coded fused representation of CT and MR images, indicates to the surgeon the location and extent of registration (in)accuracy. Integration of a small tracker camera mounted directly on the microscope permits an advantageous ergonomic way of working in the operating room. Additionally, guidance information (augmented reality) from multimodal datasets (CT, MRI, angiography) can be overlaid directly onto the surgical microscope view. The virtual simulator as a training tool in endonasal and otological skull base surgery provides an understanding of the anatomy as well as preoperative practice using real patient data. RESULTS: Using our navigation system, no major complications occurred in spite of the fact that the series included difficult skull base procedures. An improved quality in the surgical outcome was identified compared with our control group without navigation and compared with the literature. The surgical time consumption was reduced and more minimally invasive approaches were possible. According to the participants' questionnaires, the educational effect of the virtual simulator in our residency program received a high ranking.

Impact of pore size on the vascularization and osseointegration of ceramic bone substitutes in vivo

The repair of bone defects with biomaterials depends on a sufficient vascularization of the implantation site. We analyzed the effect of pore size on the vascularization and osseointegration of biphasic calcium phosphate particles, which were implanted into critical-sized cranial defects in Balb/c mice. Dense particles and particles with pore sizes in the ranges 40-70, 70-140, 140-210, and 210-280 mum were tested (n = 6 animals per group). Angiogenesis, vascularization, and leukocyte-endothelium interactions were monitored for 28 days by intravital microscopy. The formation of new bone and the bone-interface contact (BIC) were determined histomorphometrically. Twenty-eight days after implantation, the functional capillary density was significantly higher with ceramic particles whose pore sizes exceeded 140 mum [140-210 mum: 6.6 (+/-0.8) mm/mm(2); 210-280 mum: 7.3 (+/-0.6) mm/mm(2)] than with those whose pore sizes were lesser than 140 mum [40-70 mum: 5.3 (+/-0.4) mm/mm(2); 70-140 mum: 5.6 (+/-0.3) mm/mm(2)] or with dense particles [5.7 (+/-0.8) mm/mm(2)]. The volume of newly-formed bone deposited within the implants increased as the pore size increased [40-70 mum: 0.07 (+/-0.02) mm(3); 70-140 mum: 0.10 (+/-0.06) mm(3); 140-210 mum: 0.13 (+/-0.05) mm(3); 210-280 mum: 0.15 (+/-0.06) mm(3)]. Similar results were observed for the BIC. The data demonstrates pore size to be a critical parameter governing the dynamic processes of vascularization and osseointegration of bone substitutes. (c) 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007.

The impact of different nanoparticle surface chemistry and size on uptake and toxicity in a murine macrophage cell line

This study investigated the uptake, kinetics and cellular distribution of different surface coated quantum dots (QDs) before relating this to their toxicity. J774.A1 cells were treated with organic, COOH and NH2 (PEG) surface coated QDs (40 nM). Model 20 nm and 200 nm COOH-modified coated polystyrene beads (PBs) were also examined (50 microg ml(-1)). The potential for uptake of QDs was examined by both fixed and live cell confocal microscopy as well as by flow cytometry over 2 h. Both the COOH 20 nm and 200 nm PBs were clearly and rapidly taken up by the J774.A1 cells, with uptake of 20 nm PBs being relatively quicker and more extensive. Similarly, COOH QDs were clearly taken up by the macrophages. Uptake of NH2 (PEG) QDs was not detectable by live cell imaging however, was observed following 3D reconstruction of fixed cells, as well as by flow cytometry. Cells treated with organic QDs, monitored by live cell imaging, showed only a small amount of uptake in a relatively small number of cells. This uptake was insufficient to be detected by flow cytometry. Imaging of fixed cells was not possible due to a loss in cell integrity related to cytotoxicity. A significant reduction (p<0.05) in the fluorescent intensity in a cell-free environment was found with organic QDs, NH2 (PEG) QDs, 20 nm and 200 nm PBs at pH 4.0 (indicative of an endosome) after 2 h, suggesting reduced stability. No evidence of exocytosis was found over 2 h. These findings confirm that surface coating has a significant influence on the mode of NP interaction with cells, as well as the subsequent consequences of that interaction.

Investigation into the impact of grain boundaries, film interface, and crystallographic orientation on the ionic conductivity of thin film gadolinium-doped ceria

The research reported in this dissertation investigates the impact of grain boundaries, film interface, and crystallographic orientation on the ionic conductivity of thin film Gd-doped CeO2 (GDC). Chapter 2 of this work addresses claims in the literature that submicron grain boundaries have the potential to dramatically increase the ionic conductivity of GDC films. Unambiguous testing of this claim requires directly comparing the ionic conductivity of single-crystal GDC films to films that are identical except for the presence of submicron grain boundaries. In this work techniques have been developed to grow GDC films by RF magnetron sputtering from a GDC target on single crystal r plane sapphire substrates. These techniques allow the growth of films that are single crystals or polycrystalline with 80 nm diameter grains. The ionic conductivities of these films have been measured and the data shows that the ionic conductivity of single crystal GDC is greater than that of the polycrystalline films by more than a factor of 4 over the 400-700°C temperature range. Chapter 3 of this work investigates the ionic conductivity of surface and interface regions of thin film Gd-doped CeO2. In this study, single crystal GDC films have been grown to thicknesses varying from 20 to 500 nm and their conductivities have been measured in the 500-700°C temperature range. Decreasing conductivity with decreasing film thickness was observed. Analysis of the conductivity data is consistent with the presence of an approximately 50 nm layer of less conductive material in every film. This study concludes that the surface and interface regions of thin film GDC are less conductive than the bulk single crystal regions, rather than being highly conductive paths. Chapter 4 of this work investigates the ionic conductivity of thin film Gd-doped CeO2 (GDC) as a function of crystallographic orientation. A theoretical expression has been developed for the ionic conductivity of the [100] and [110] directions in single crystal GDC. This relationship is compared to experimental data collected from a single crystal GDC film. The film was grown to a thickness of _300 nm and its conductivity measured along the [100] and [110] orientations in the 500-700°C temperature range. The experimental data shows no statistically significant difference in the conductivities of the [100] and [110] directions in single crystal GDC. This result agrees with the theoretical model which predicts no difference between the conductivities of the two directions.

Impact of previous virological treatment failures and adherence on the outcome of antiretroviral therapy in 2007

BACKGROUND: Combination antiretroviral treatment (cART) has been very successful, especially among selected patients in clinical trials. The aim of this study was to describe outcomes of cART on the population level in a large national cohort. METHODS: Characteristics of participants of the Swiss HIV Cohort Study on stable cART at two semiannual visits in 2007 were analyzed with respect to era of treatment initiation, number of previous virologically failed regimens and self reported adherence. Starting ART in the mono/dual era before HIV-1 RNA assays became available was counted as one failed regimen. Logistic regression was used to identify risk factors for virological failure between the two consecutive visits. RESULTS: Of 4541 patients 31.2% and 68.8% had initiated therapy in the mono/dual and cART era, respectively, and been on treatment for a median of 11.7 vs. 5.7 years. At visit 1 in 2007, the mean number of previous failed regimens was 3.2 vs. 0.5 and the viral load was undetectable (<50 copies/ml) in 84.6% vs. 89.1% of the participants, respectively. Adjusted odds ratios of a detectable viral load at visit 2 for participants from the mono/dual era with a history of 2 and 3, 4, >4 previous failures compared to 1 were 0.9 (95% CI 0.4-1.7), 0.8 (0.4-1.6), 1.6 (0.8-3.2), 3.3 (1.7-6.6) respectively, and 2.3 (1.1-4.8) for >2 missed cART doses during the last month, compared to perfect adherence. From the cART era, odds ratios with a history of 1, 2 and >2 previous failures compared to none were 1.8 (95% CI 1.3-2.5), 2.8 (1.7-4.5) and 7.8 (4.5-13.5), respectively, and 2.8 (1.6-4.8) for >2 missed cART doses during the last month, compared to perfect adherence. CONCLUSIONS: A higher number of previous virologically failed regimens, and imperfect adherence to therapy were independent predictors of imminent virological failure.

Pelagic molybdenum concentration anomalies and the impact of sediment resuspension on the molybdenum budget in two tidal systems of the North Sea

The seasonal dynamics of molybdenum (Mo) were studied in the water column of two tidal basins of the German Wadden Sea (Sylt-Rømø and Spiekeroog) between 2007 and 2011. In contrast to its conservative behaviour in the open ocean, both, losses of more than 50% of the usual concentration level of Mo in seawater and enrichments up to 20% were observed repeatedly in the water column of the study areas. During early summer, Mo removal by adsorption on algae-derived organic matter (e.g. after Phaeocystis blooms) is postulated to be a possible mechanism. Mo bound to organic aggregates is likely transferred to the surface sediment where microbial decomposition enriches Mo in the pore water. First δ98/95Mo data of the study area disclose residual Mo in the open water column being isotopically heavier than MOMo (Mean Ocean Molybdenum) during a negative Mo concentration anomaly, whereas suspended particulate matter shows distinctly lighter values. Based on field observations a Mo isotope enrichment factor of ε = −0.3‰ has been determined which was used to argue against sorption on metal oxide surfaces. It is suggested here that isotope fractionation is caused by biological activity and association to organic matter. Pelagic Mo concentration anomalies exceeding the theoretical salinity-based concentration level, on the other hand, cannot be explained by replenishment via North Sea waters alone and require a supply of excess Mo. Laboratory experiments with natural anoxic tidal flat sediments and modelled sediment displacement during storm events suggest fast and effective Mo release during the resuspension of anoxic sediments in oxic seawater as an important process for a recycling of sedimentary sulphide bound Mo into the water column.

Impact of loading displacements on SLR-derived parameters and on the consistency between GNSS and SLR results

Displacements of the Earth’s surface caused by tidal and non-tidal loading forces are relevant in high-precision space geodesy. Some of the corrections are recommended by the international scientific community to be applied at the observation level, e.g., ocean tidal loading (OTL) and atmospheric tidal loading (ATL). Non-tidal displacement corrections are in general recommended not to be applied in the products of the International Earth Rotation and Reference Systems Service, in particular atmospheric non-tidal loading (ANTL), oceanic and hydrological non-tidal corrections. We assess and compare the impact of OTL, ATL and ANTL on SLR-derived parameters by reprocessing 12 years of SLR data considering and ignoring individual corrections. We show that loading displacements have an influence not only on station long-term stability, but also on geocenter coordinates, Earth Rotation Parameters, and satellite orbits. Applying the loading corrections reduces the amplitudes of annual signals in the time series of geocenter and station coordinates. The general improvement of the SLR station 3D coordinate repeatability when applying OTL, ATL and ANTL corrections are 19.5 %, 0.2 % and 3.3 % respectively, w.r.t. the solutions without loading corrections. ANTL corrections play a crucial role in the combination of optical (SLR) and microwave (GNSS, VLBI, DORIS) space geodetic observation techniques, because of the so-called Blue-Sky effect: SLR measurements can be carried out only under cloudless sky conditions—typically during high air pressure conditions, when the Earth’s crust is deformed, whereas microwave observations are weather-independent. Thus, applying the loading corrections at the observation level improves SLR-derived products as well as the consistency with microwave-based results. We assess the Blue-Sky effect on SLR stations and the consistency improvement between GNSS and SLR solutions when ANTL corrections are included. The omission of ANTL corrections may lead to inconsistencies between SLR and GNSS solutions of up to 2.5 mm for inland stations. As a result, the estimated GNSS–SLR coordinate differences correspond better to the local ties at the co-located stations when applying ANTL corrections.

Impact of changes in haematocrit level and platelet count on thromboelastometry parameters

INTRODUCTION To what extent haematocrit levels (Hct) and platelet counts (PLT) influence the measurement of parameters of thromboelastometry when assessed with the ROTEM® device is unclear. We investigated to what extent thromboelastometry measurements depend on Hct and PLT. MATERIALS AND METHODS Whole blood samples were taken for in-vitro preparations of mixtures with three different levels of PLT and a varying Hct. Maximum clot firmness (MCF), clotting time (CT), clot formation time (CFT) and alpha angle (α) for INTEM, EXTEM, FIBTEM and APTEM was recorded. RESULTS Measurements depended substantially on Hct and PLT. MCF readings were systematically lower with increasing Hct (0.2 vs. 0.4: -7.8 (-8.3 to -7.2); p<0.001, 0.2 vs. 0.55: -14.5 (-17.3 to -14.3); p<0.001) but higher with increasing PLT (50 vs. 125×10(9)/l: 8.2 (4.2 to 12.3); p=0.005, 50 vs. 250×10(9)/l: 12.0 (7.2 to 16.8); p=0.002). CT readings were systematically higher with increasing Hct (0.2 vs. 0.4: 9.2 (6.2 to 12.1); p=0.001, 0.2 vs. 0.55: 38.2 (21.5 to 54.9); p=0.003) while increasing PLT had no influence. CFT readings were also systematically higher with increasing Hct (0.2 vs. 0.4: 83.8 (40.2 to 127.6); p=0.006, 0.2 vs. 0.55: 226.2 (110.7 to 341.7); p=0.006) but systematically lower with increasing PLT (50 vs. 125×10(9)/l: -144.0 (-272.3 to -15.6); p=0.036, 50 vs. 250×10(9)/l: -189.2 (-330.4 to -48.0); p=0.02); readings of the alpha angle showed a similar pattern. CONCLUSIONS Our results suggest that readings of thromboelastometry parameters need to be adjusted by Hct and PLT to avoid potential confounding and miss-interpretations in clinical practice.

A study of the impact of cigarette advertising on adolescent susceptibility to smoking among 5th-, 8th-, and 12th-grade students in Hempstead and Hitchcock Independent School Districts

This study assessed the impact of cigarette advertising on adolescent susceptibility to smoking in the Hempstead and Hitchcock Independent School Districts. A convenience sample of 217 youths, 10-19 years of age was recruited in the study. Students completed both a paper-and-pencil and a computer-aided questionnaire in April 1996. Adolescents were defined as susceptible to smoking if they could not definitely rule out the possibility of future smoking. For the analysis, an index was devised: a 5-point index of an individual's receptivity to cigarette advertising. The index is determined by the number of positive responses to five survey items (recognizing cigarette brand logos, recognizing cigarette advertisement's pictures, recognizing cigarette brand slogans, evaluating adolescent attitudes toward cigarette advertising, and the degree to which adolescents were exposed to cigarette advertisements). Using logistic regression, we assessed the independent importance of the index in predicting susceptibility to smoking and ever smoking after adjusting for sociodemographic variables, perceived school performance and family composition. Of students surveyed, 54.4% of students appeared to have started the smoking uptake process as measured by susceptibility to smoking. Camel was recognized by the majority of students (88%), followed by Marlboro (41.5%) and Newport (40.1%). The pattern for recognition of the cigarette advertisements was the same as the pattern of market for cigarette. Advertisement featuring the cartoon character Joe Camel was significantly more appealing to adolescents than were advertisements with human models, with animal models, and with text only (p $<$ 0.001). Text only advertisement was significantly less appealing than other types of advertisements. The cigarette advertisement with White models (Marlboro) had significantly higher appeal to White students than to African-American students (p $<$ 0.001). The cigarette advertisement featuring African-American models (Virginia Slims) was significantly more appealing to African-American students than other ethnic groups (p $<$ 0.001). Receptivity to cigarette advertising was to be an important concurrent predictor of past smoking experience and intention to smoke in the future. Adolescents who scored in the fourth quartile of the Index of Receptivity to Cigarette Advertising were 7.54 (95% confidence interval (CI) = 1.92-29.56) times as likely to be susceptible to smoking, and were 4.56 (95% CI = 1.55-13.38) times as likely to have tried smoking, as those who scored in the first quartile of the Index. The findings confirmed the hypothesis that cigarette advertising may be a strong current influence in encouraging adolescents to initiate the smoking uptake process than sociodemographic variables, perceived school performance and family composition. ^